792 
Severe Hyperlactatemia Complicating ART with Stavudine First-line Therapy in South Africa: Incidence, Risk Factors, and Outcomes
Meg Osler*1,2, Meg Osler*1,2, D Stead3, K Rebe2,3, K Rebe2,3, A Boulle1,2, A Boulle1,2, G Meintjes2,3, and G Meintjes2,3
1Provincial Dept of Hlth, Cape Town, South Africa; 2Univ of Cape Town, South Africa; and 3GF Jooste Hosp, Cape Town, South Africa
Background: In the
public sector ART program in South
Africa, the first-line regimen is stavudine (d4T) + lamivudine (3TC)
+ a non-nucleoside reverse transcriptase inhibitor (NNRTI). This study,
undertaken at a referral center for 6 ART clinics, documented the referral rate,
risk factors, and outcomes for patients presenting with severe hyperlactatemia (SHL).
Methods: All cases presenting
with lactate levels ≥5 mmol/L related to ART
from August 2003 to November 2005 were retrospectively reviewed. The cumulative
exposure to ART among patients attending the 6 ART clinics was calculated to
derive an estimated rate of referral. Associations between risk factors and
acute mortality were explored using logistic regression. In a matched
case-control study with incidence density sampling, 55 cases from this cohort were
matched with 110 controls according to clinic and month starting ART. Conditional
logistic regression was used to illicit associations between risk factors and
SHL.
Results: There were
73 patients who presented with SHL (69 were
females and median age was 32.5 years). Patients had been on ART for a median
of 7 months (IQR 5 to 9). During this period there was a cumulative exposure to
ART of 7080 patient-years at all 6 ART clinics resulting in an estimated rate
of referral for SHL of 10/1000 treatment years. Of the total, 11 patients (15%)
died acutely and 2 died subsequently. SHCO3 below 15 mmol/L was the only risk factor consistently associated
with acute mortality in univariate and multivariate
modeling (OR = 35, p = 0.004,
adjusted for age). There were 29 selected cases that rechallenged
on zidovudine (AZT)/3TC (all had sHCO3 ≥14.1
mmol/L) were followed for a median of 10 months with lactate
monitoring. Only 1 developed recurrent hyperlactatemia.
In the case-control study multivariate analysis, a baseline weight >60 kg,
female gender and a low nadir CD4 count all increased the risk of acquiring SHL
when controlling for age. Compared to people with a baseline weight <60 kg,
those between 60 and 74 kg were at 5.1 times higher risk for SHL (95%CI 1.48 to
17.43) while those >75 kg had a 12.2-fold increased risk (95%CI 3.25 to
45.85). The odds ratio for females was 33.6 (95%CI 4.82-234.3) while each
additional nadir CD4 cell/mm3 decreased the risk of SHL by 1% (OR = 0.99
95%CI 0.98 to 0.99).
Conclusions: A rate of
referral for SHL of 10/1000 treatment years was documented. Female gender, high
baseline weight, and low nadir CD4 count were risk factors for SHL. Rechallenge with AZT in selected cases seems safe where lactate can be
monitored.
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